METABOLISM OF FOOD-DERIVED HETEROCYCLIC AMINES IN HUMAN AND RABBIT-TISSUES BY P4503A PROTEINS IN THE PRESENCE OF FLAVONOIDS

The ability of human and rabbit gastrointestinal-tract microsomes to m etabolize the heterocyclic amine 2-amino-3,4-dimethylimidazo[4,5-f]qui noline (MeIQ) to a mutagen was determined with the Ames test. When hum an jejunal and ileal microsomes were used as the metabolic activation source, MeIQ produced 1675 and 388 revertants/mg of microsomal protein , respectively, and this increased to 29,230 and 17,963 revertants/mg of microsomal protein, respectively, in the presence of 100-mu-M alpha -naphthoflavone. MeIQ in the presence of control rabbit duodenal, jeju nal, and ileal microsomes produced 2304 +/- 1018, 988 +/- 386, and 444 +/- 134 (mean +/- SD, four samples) revertants/mg of microsomal prote in, respectively. In the presence of alpha-naphthoflavone (100-mu-M), these activities increased > 7-fold. P4503A proteins were detectable o n Western blots of microsomes prepared from both human and rabbit smal l intestine. Further, rifampicin-induced rabbit hepatic-microsomal act ivation of MeIQ was completely inhibited at low concentrations of alph a-naphthoflavone, but at higher concentrations (ie., 100-mu-M) this re turned to control levels. Flavone also caused a marked stimulation of MeIQ activation in human and rabbit gastrointestinal-tract microsomes. The aforementioned data suggest that flavonoids markedly increase the ability of P4503A isozymes to activate heterocyclic amines to mutagen s in the Ames test.